verse endocrine effects topical corticosteroids, including fluticasone propionate lotion, can produce reversible hpa axis suppression with the potential for glucocorticoid insufficiency. risk factors that predispose to hpa axis suppression include the use of high-potency topical corticosteroids, large treatment surface areas, prolonged use, use under occlusion, concomitant use of more than one corticosteroid-containing product, altered skin barrier, and liver failure. pediatric patients may be at greater risk of hpa axis suppression due to their higher skin surface area to body mass ratios [ see use in specific populations ( 8.4 ) ]. hpa axis suppression may occur during or after withdrawal of treatment. if hpa axis suppression is suspected, gradually withdraw the drug, reduce the frequency of application, or substitute a less potent topical corticosteroid. evaluation of hpa axis suppression may be done by using the cosyntropin stimulation test. the effects of fluticasone propionate lotion on hpa axis function in pediatric patients were investigated in two trials. among a total of 89 evaluable subjects from the two trials who were treated with fluticasone propionate lotion twice daily for 3 to 4 weeks, a single subject with >90% body surface area treated showed laboratory evidence of transient suppression immediately post-treatment. the post cosyntropin stimulation test serum cortisol returned to a normal level (22.1 μg/dl) within one week of the final treatment visit [ see use in specific populations ( 8.4 ) and clinical pharmacology ( 12.2 ) ]. cushing’s syndrome, hyperglycemia, and unmasking of latent diabetes mellitus can also result from systemic absorption of topical corticosteroids. use of more than one corticosteroid-containing product at the same time may increase the total systemic absorption of topical corticosteroids. 5.2 local adverse reactions fluticasone propionate lotion may cause local adverse reactions, including skin atrophy [ see adverse reactions ( 6.1 , 6.2 ) ]. the risk is greater with use under occlusion and with higher potency products. fluticasone propionate lotion contains the excipient imidurea which releases formaldehyde as a breakdown product. formaldehyde may cause allergic sensitization or irritation upon contact with the skin. avoid using fluticasone propionate lotion in individuals with hypersensitivity to formaldehyde as it may prevent healing or worsen dermatitis. if irritation develops, discontinue fluticasone propionate lotion and institute appropriate therapy. allergic contact dermatitis allergic contact dermatitis with corticosteroids is usually diagnosed by observing a failure to heal rather than noticing a clinical exacerbation. such an observation can be corroborated with appropriate diagnostic patch testing. discontinue fluticasone propionate lotion if appropriate. 5.3 concomitant skin infections if skin infections are present or develop at the treatment site, an appropriate antimicrobial agent should be used. if a favorable response does not occur promptly, discontinue use of fluticasone propionate lotion until the infection has been adequately controlled.

not for ophthalmic, oral, or intravaginal use. ( 2 )

sone propionate lotion by 196 adult and 242 pediatric patients, the total incidence of adverse reactions considered drug related by investigators was approximately 4%. these were local cutaneous reactions, usually mild and self-limiting, and consisted primarily of burning/stinging (2%). all other drug-related events occurred with an incidence of less than 1%, and included were contact dermatitis, exacerbation of atopic dermatitis, folliculitis of legs, pruritus, pustules on arm, rash, and skin infection. see table 1. the incidence of adverse reactions between the 242 pediatric subjects (age 3 months to < 17 years) and 196 adult subjects (17 years or older) was similar (4% and 5%, respectively). table 1: adverse reactions from controlled clinical trials (n=438) adverse reactions fluticasone propionate lotion n=221 vehicle n=217 burning/stinging skin 4 (2%) 3 (1%) contact dermatitis 0 1 (<1%) exacerbation of atopic dermatitis 0 1 (<1%) folliculitis of legs 2 (<1%) 0 irritant contact dermatitis 0 1 (<1%) pruritus 1 (<1%) 1 (<1%) pustules on arms 1 (<1%) 0 rash 1 (<1%) 2 (<1%) skin infection 0 3 (1%) during the clinical trials, eczema herpeticum occurred in a 33-year old male patient treated with fluticasone propionate lotion. table 2 summarizes all adverse events by body system that occurred in at least 1% of patients in either the drug or vehicle group in the phase 3 controlled clinical trials. table 2: adverse events occurring in ≥1% of patients from either arm from controlled clinical trials (n=438) body system fluticasone propionate lotion (n=221) vehicle lotion (n=217) any adverse event 77 (35%) 82 (38%) skin burning and stinging 4 (2%) 3 (1%) pruritus 3 (1%) 5 (2%) rash 2 (<1%) 3 (1%) skin infection 0 3 (1%) ear, nose, throat common cold 9 (4%) 5 (2%) ear infection 3 (1%) 3 (1%) nasal sinus infection 2 (<1%) 4 (2%) rhinitis 1 (<1%) 3 (1%) upper respiratory tract infection 6 (3%) 7 (3%) gastrointestinal normal tooth eruption 2 (<1%) 3 (1%) diarrhea 3 (1%) 0 vomiting 3 (1%) 2 (<1%) lower respiratory cough 7 (3%) 6 (3%) influenza 5 (2%) 0 wheeze 0 3 (1%) neurology headache 4 (2%) 5 (2%) non-site specific fever 8 (4%) 8 (4%) seasonal allergy 2 (<1%) 3 (1%) 6.2 clinical trials experience: pediatric open label trials in an open label hpa axis suppression trial of 44 pediatric subjects (ages ≥3 months to ≤6 years) fluticasone propionate lotion was applied twice daily (rather than the indicated dosing regimen of once daily) to at least 35% of body surface area for 3 or 4 weeks. subjects whose lesions cleared after 2 or 3 weeks of treatment continued to apply fluticasone propionate lotion for an additional week. the overall incidence of adverse reactions was 14%. these were local, cutaneous reactions and included dry skin (7%), stinging at application site (5%), and excoriation (2%). additionally, a 4-month-old patient treated with fluticasone propionate lotion had marked elevations of the hepatic enzymes ast and alt. [ see use in specific populations ( 8.4 ) ] in another open label hpa axis suppression trial in which fluticasone propionate lotion was also applied twice daily (rather than the indicated dosing regimen of once daily), 56 pediatric subjects (ages ≥3 months to 12 months), were enrolled [ see use in specific populations ( 8.4 ) ]. the adverse reactions included 2 cases of herpes simplex at the application site (3.6%) and 3 cases of bacterial skin infections (5.4%). 6.3 postmarketing experience the following local adverse reactions have been identified during post-approval use of fluticasone propionate lotion: erythema, edema/swelling, and bleeding. the following systemic adverse reactions have been identified during post-approval use of fluticasone propionate cream and fluticasone propionate ointment: immunosuppression/ pneumocystis jirovecii pneumonia/leukopenia/thrombocytopenia; hyperglycemia/ glycosuria; cushing syndrome; generalized body edema/blurred vision; and acute urticarial reaction (edema, urticaria, pruritus, and throat swelling). the following local adverse reactions have also been reported with the use of topical corticosteroids, and they may occur more frequently with the use of occlusive dressings or higher potency corticosteroids. these reactions include: acneiform eruptions, hypopigmentation, perioral dermatitis, skin atrophy, striae, hypertrichosis and miliaria. because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.

female rats in two embryofetal development studies (one study administered fluticasone propionate from gestation days 6 to 15 and the other study from gestation days 7 to 17). in the presence of maternal toxicity, fetal effects noted at 100 μg/kg/day (less than the mrhd in adults based on body surface area comparisons) included decreased fetal weights, omphalocele, cleft palate, and retarded skeletal ossification. no treatment related effects on embryofetal toxicity or teratogenicity were noted at 10 μg/kg/day (less than the mrhd in adults based on body surface area comparisons). subcutaneous doses of 0.08, 0.57 and 4 μg/kg/day of fluticasone propionate were administered to pregnant female rabbits from gestation days 6 to 18. fetal effects noted at 4 μg/kg/day (less than the mrhd in adults based on body surface area comparisons) included decreased fetal weights, cleft palate and retarded skeletal ossification. no treatment related effects on embryofetal toxicity or teratogenicity were noted at 0.57 μg/kg/day (less than the mrhd in adults based on body surface area comparisons). oral doses of 3, 30 and 300 μg/kg/day fluticasone propionate were administered to pregnant female rabbits from gestation days 8 to 20. no fetal or teratogenic effects were noted at oral doses up to 300 μg/kg/day (less than the mrhd in adults based on body surface area comparisons) in this study. however, no fluticasone propionate was detected in the plasma in this study, consistent with the established low bioavailability following oral administration. fluticasone propionate crossed the placenta following administration of a subcutaneous or an oral dose of 100 μg/kg tritiated fluticasone propionate to pregnant rats. 8.3 nursing mothers systemically administered corticosteroids appear in human milk and can suppress growth, interfere with endogenous corticosteroid production, or cause other untoward effects. it is not known whether topical administration of corticosteroids could result in sufficient systemic absorption to produce detectable quantities in human milk. because many drugs are excreted in human milk, caution should be exercised when fluticasone propionate lotion is administered to a nursing woman. 8.4 pediatric use fluticasone propionate lotion may be used in pediatric patients as young as 3 months of age. the safety and effectiveness of fluticasone propionate lotion in pediatric patients below 3 months of age have not been established. because of a higher ratio of skin surface area to body mass, pediatric patients are at a greater risk than adults of systemic effects when treated with topical drugs. they are, therefore, also at greater risk of hpa axis suppression and adrenal insufficiency upon the use of topical corticosteroids [ see warnings and precautions ( 5.1 ) ]. in an hpa axis suppression trial, none of the 40 evaluable pediatric subjects, 4 months old to < 6 years old, with moderate to severe atopic dermatitis covering ≥ 35% body surface area (bsa) who were treated with an exaggerated dosing regimen (twice daily) of fluticasone propionate lotion experienced adrenal suppression (defined as a 30-minute post-stimulation cortisol level ≤18 micrograms/dl) [ see warnings and precautions ( 5.1 ) and clinical pharmacology ( 12.2 ) ]. in another hpa axis suppression trial, one of 49 (2%) evaluable pediatric subjects, 3 months to 11 months old, with moderate to severe atopic dermatitis covering ≥ 35% body surface area (bsa) who applied an exaggerated dosing regimen (twice daily) of fluticasone propionate lotion experienced reversible adrenal suppression (defined as a 30-minute post-stimulation cortisol level ≤18 micrograms/dl) following 4 weeks of therapy [ see warnings and precautions ( 5.1 ) and clinical pharmacology ( 12.2 ) ] . systemic effects such as cushing's syndrome, linear growth retardation, delayed weight gain, and intracranial hypertension have been reported in pediatric patients, especially those with prolonged exposure to large doses of high-potency topical corticosteroids, or concomitant use of more than one corticosteroid product. local adverse reactions including skin atrophy have also been reported with use of topical corticosteroids in pediatric patients. parents of pediatric patients should be advised not to use this medication in the treatment of diaper dermatitis unless directed by a physician. fluticasone propionate lotion should not be applied in the diaper areas as diapers or plastic pants may constitute occlusive dressing. 8.5 geriatric use a limited number of patients above 65 years of age have been treated with fluticasone propionate lotion in us and non-us clinical trials. specifically only 8 patients above 65 years of age were treated with fluticasone propionate lotion in controlled clinical trials. the number of patients is too small to permit separate analyses of efficacy and safety.

l development studies (one study administered fluticasone propionate from gestation days 6 to 15 and the other study from gestation days 7 to 17). in the presence of maternal toxicity, fetal effects noted at 100 μg/kg/day (less than the mrhd in adults based on body surface area comparisons) included decreased fetal weights, omphalocele, cleft palate, and retarded skeletal ossification. no treatment related effects on embryofetal toxicity or teratogenicity were noted at 10 μg/kg/day (less than the mrhd in adults based on body surface area comparisons). subcutaneous doses of 0.08, 0.57 and 4 μg/kg/day of fluticasone propionate were administered to pregnant female rabbits from gestation days 6 to 18. fetal effects noted at 4 μg/kg/day (less than the mrhd in adults based on body surface area comparisons) included decreased fetal weights, cleft palate and retarded skeletal ossification. no treatment related effects on embryofetal toxicity or teratogenicity were noted at 0.57 μg/kg/day (less than the mrhd in adults based on body surface area comparisons). oral doses of 3, 30 and 300 μg/kg/day fluticasone propionate were administered to pregnant female rabbits from gestation days 8 to 20. no fetal or teratogenic effects were noted at oral doses up to 300 μg/kg/day (less than the mrhd in adults based on body surface area comparisons) in this study. however, no fluticasone propionate was detected in the plasma in this study, consistent with the established low bioavailability following oral administration. fluticasone propionate crossed the placenta following administration of a subcutaneous or an oral dose of 100 μg/kg tritiated fluticasone propionate to pregnant rats.

rnings and precautions ( 5.1 ) and clinical pharmacology ( 12.2 ) ]. in another hpa axis suppression trial, one of 49 (2%) evaluable pediatric subjects, 3 months to 11 months old, with moderate to severe atopic dermatitis covering ≥ 35% body surface area (bsa) who applied an exaggerated dosing regimen (twice daily) of fluticasone propionate lotion experienced reversible adrenal suppression (defined as a 30-minute post-stimulation cortisol level ≤18 micrograms/dl) following 4 weeks of therapy [ see warnings and precautions ( 5.1 ) and clinical pharmacology ( 12.2 ) ] . systemic effects such as cushing's syndrome, linear growth retardation, delayed weight gain, and intracranial hypertension have been reported in pediatric patients, especially those with prolonged exposure to large doses of high-potency topical corticosteroids, or concomitant use of more than one corticosteroid product. local adverse reactions including skin atrophy have also been reported with use of topical corticosteroids in pediatric patients. parents of pediatric patients should be advised not to use this medication in the treatment of diaper dermatitis unless directed by a physician. fluticasone propionate lotion should not be applied in the diaper areas as diapers or plastic pants may constitute occlusive dressing.

ily) for at least 3 to 4 weeks were assessed for hpa axis suppression. the mean bsa treated was 65%. none of the 40 evaluable subjects were suppressed. the criterion for hpa axis suppression was a serum cortisol level of less than or equal to 18 micrograms per deciliter at 30-minutes after cosyntropin stimulation. another open label hpa axis suppression trial (trial b) enrolled 56 pediatric subjects (ages 3 months to 11 months) with moderate to severe atopic dermatitis covering ≥ 35% bsa. subjects were treated with an exaggerated dosing regimen for of fluticasone propionate lotion, 0.05% twice daily over a period of 3 or 4 weeks. the mean bsa treated was 54%. out of 56 subjects, 49 were considered evaluable with respect to their adrenal axis function post-treatment. one of 49 subjects showed laboratory evidence of suppression immediately post treatment. the criterion for hpa axis suppression was a serum cortisol level of less than or equal to 18 micrograms per deciliter at 30-minutes after cosyntropin stimulation. repeated test one week later showed the post cosyntropin stimulation testing serum cortisol returned to normal level (22.1 μg/dl). this 4-month old subject had a baseline treatment bsa of 94% and was reported to have received 100% of the twice-daily applications of fluticasone propionate lotion, 0.05% over the 27 day treatment period. 12.3 pharmacokinetics absorption the extent of percutaneous absorption of topical corticosteroids is determined by many factors, including the vehicle and the integrity of the epidermal barrier. occlusive dressing enhances penetration. topical corticosteroids can be absorbed from normal intact skin. inflammation and/or other disease processes in the skin increase percutaneous absorption. plasma fluticasone levels were measured in a subset of subjects 2 to 5 years and 11 months of age in hpa axis suppression trial (trial a) described above. a total of 13 (62%) of 21 subjects tested had measurable fluticasone at the end of 3 to 4 weeks of treatment. the mean ± sd fluticasone plasma concentration was 0.16 ± 0.23 ng/ml. three subjects aged 3, 4, and 4 years had fluticasone concentrations over 0.30 ng/ml, with one of them having a concentration of 0.82 ng/ml. no data were obtained for subjects < 2 years of age. distribution the percentage of fluticasone propionate bound to human plasma proteins averaged 91%. fluticasone propionate is weakly and reversibly bound to erythrocytes. fluticasone propionate is not significantly bound to human transcortin. metabolism no metabolites of fluticasone propionate were detected in an in vitro study of radiolabeled fluticasone propionate incubated in a human skin homogenate. fluticasone propionate is metabolized in the liver by cytochrome p450 3a4-mediated hydrolysis of the 5-fluoromethyl carbothiolate grouping. this transformation occurs in 1 metabolic step to produce the inactive 17β-carboxylic acid metabolite, the only known metabolite detected in man. this metabolite has approximately 2000 times less affinity than the parent drug for the glucocorticoid receptor of human lung cytosol in vitro and negligible pharmacological activity in animal studies. other metabolites detected in vitro using cultured human hepatoma cells have not been detected in man.

a proteins averaged 91%. fluticasone propionate is weakly and reversibly bound to erythrocytes. fluticasone propionate is not significantly bound to human transcortin. metabolism no metabolites of fluticasone propionate were detected in an in vitro study of radiolabeled fluticasone propionate incubated in a human skin homogenate. fluticasone propionate is metabolized in the liver by cytochrome p450 3a4-mediated hydrolysis of the 5-fluoromethyl carbothiolate grouping. this transformation occurs in 1 metabolic step to produce the inactive 17β-carboxylic acid metabolite, the only known metabolite detected in man. this metabolite has approximately 2000 times less affinity than the parent drug for the glucocorticoid receptor of human lung cytosol in vitro and negligible pharmacological activity in animal studies. other metabolites detected in vitro using cultured human hepatoma cells have not been detected in man.

aberration assay and human lymphocyte chromosome aberration assay) and one in vivo genotoxicity test (mouse micronucleus assay). no evidence of impairment of fertility or effect on mating performance was observed in a fertility and general reproductive performance study conducted in male and female rats at subcutaneous doses up to 50 μg/kg/day (less than the mrhd in adults based on body surface area comparisons).

n lymphocyte chromosome aberration assay) and one in vivo genotoxicity test (mouse micronucleus assay). no evidence of impairment of fertility or effect on mating performance was observed in a fertility and general reproductive performance study conducted in male and female rats at subcutaneous doses up to 50 μg/kg/day (less than the mrhd in adults based on body surface area comparisons).

fluticasone propionate lotion vehicle study 1 9/45 (20%) 0/37 (0%) study 2 7/44 (16%) 1/43 (2%)

ected by the healthcare provider. local adverse reactions advise the patient to report any signs of local adverse reactions to their healthcare provider [ see warnings and precautions ( 5.2 ) ]. • advise patients to report to their healthcare provider if they are allergic to formaldehyde. manufactured by padagis yeruham, israel distributed by padagis allegan, mi 49010 • www.padagis.com rev 06-22

your medical conditions, including if you: • have a skin infection at the site to be treated. you may also need medicine to treat the skin infection. • have adrenal gland problems • have liver problems • have diabetes • have thinning skin (atrophy) at the site to be treated • are allergic to formaldehyde. if you are allergic to formaldehyde, fluticasone propionate lotion may cause skin irritation, prevent your skin from healing or worsen your skin condition. • are pregnant or plan to become pregnant. it is not known if fluticasone propionate lotion will harm your unborn baby. • are breastfeeding or plan to breastfeed. it is not known if fluticasone propionate lotion can pass into your breast milk and harm your baby. tell your healthcare provider about all the medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements. especially tell your healthcare provider if you take other corticosteroid medicines by mouth or use other products on your skin that contain corticosteroids. how should i use fluticasone propionate lotion? • use fluticasone propionate lotion exactly as your healthcare provider tells you to use it. • apply a thin film of fluticasone propionate lotion to the affected area 1 time each day. gently rub into your skin. • do not bandage, cover, or wrap the treated area unless your healthcare provider tells you to. do not apply fluticasone propionate lotion to dermatitis in the diaper area unless your healthcare provider tells you to. • wash your hands after applying fluticasone propionate lotion, unless your hands are being treated. • tell your healthcare provider if your symptoms get worse with fluticasone propionate lotion or if your symptoms do not improve after 2 weeks of treatment. it is not known if fluticasone propionate lotion is safe or effective when used more than 4 weeks. what are possible side effects with fluticasone propionate lotion? fluticasone propionate lotion may cause serious side effects, including: • fluticasone propionate lotion can pass through your skin and may cause adrenal gland problems. this is more likely to happen if you use fluticasone propionate lotion for too long, use it over a large treatment area, use it with other topical medicines that contain corticosteroids, cover the treated area, or have liver failure. your healthcare provider may do blood tests to check your adrenal gland function during and after treatment with fluticasone propionate lotion. • skin problems, including skin reactions or thinning of your skin (atrophy), skin infections, and allergic reactions (allergic contact dermatitis) at the treatment site. tell your healthcare provider if you get any skin reactions such as pain, tenderness, swelling, or healing problems. the most common side effects of fluticasone propionate lotion include burning and stinging at the treatment site. these are not all the possible side effects with fluticasone propionate lotion. call your doctor for medical advice about side effects. you may report side effects to fda at 1-800-fda-1088. how should i store fluticasone propionate lotion? • store fluticasone propionate lotion at 20-25°c (68-77°f) [see usp controlled room temperature]. • do not refrigerate. • keep the bottle tightly closed. keep fluticasone propionate lotion and all medicines out of the reach of children. general information about the safe and effective use of fluticasone propionate lotion. medicines are sometimes prescribed for purposes other than those listed in a patient information leaflet. do not use fluticasone propionate lotion for a condition for which it was not prescribed. do not give fluticasone propionate lotion to other people, even if they have the same symptoms you have. it may harm them. you can ask your pharmacist or healthcare provider for information about fluticasone propionate lotion that is written for health professionals. what are the ingredients in fluticasone propionate lotion? active ingredient: fluticasone propionate inactive ingredients: anhydrous citric acid, cetomacrogol 1000, cetostearyl alcohol, dimethicone 360, imidurea, isopropyl myristate, methylparaben, mineral oil, propylene glycol, propylparaben, purified water, and sodium citrate for more information, go to www.padagis.com or call 1-866-634-9120. this patient information has been approved by the u.s. food and drug administration manufactured by padagis, yeruham, israel distributed by padagis allegan, mi 49010 • www.padagis.com rev 06-22